Roderick St. James (Hugh Jackman) is a pampered pet rat who lives in Kensington. When his owners go on vacation, that's when Roddy comes out to play. But one day, a common sewer rat named Sid (Shane Richie) comes spewing out the sink. That's when he decides to stay. And all of this goes on as the Soccer World Cup is playing, with England in a match against Germany. In one scene where it shows Sid watching the game, it announces the teams, with him cheering on England and booing Germany and throwing a hot dog at the TV. Roddy tries to get rid of Sid by telling him that the toilet is actually a jacuzzi, but Sid is no idiot. He plays along and tricks Roddy into going into the 'jacuzzi'. When he reaches the end of the pipes, he enters a rat version of London, complete with homemade Big Ben clocktower and everything. That's where he meets Rita (Kate Winslet) a streetwise scavenging rat who works the tunnels in her boat The Jammy Dodger. Initially, Rita dislikes Roddy, but she takes him on as her enemy The Toad (Ian McKellen) sends his 2 minions Spike (Andy Serkis) and Whitey (Bill Nighy) after her because she has stolen back her father's prized ruby. The Toad hates all rodents to the point of obsession, blaming them from his fall from the nice life, in the movie, he was once Prince Charles' pet. He decides to have them frozen with liquid nitrogen. However this plan fails, as during their escape, Rita steals the master control belt to control the floodgates. The Toad's plan is to open the floodgates during the World Cup's halftime, drowning the rats and the city in sewage. Then he can repopulate the city with his own tadpole offspring.
Roddy discovers that the ruby Rita has is a fake and smashes it right in front of her. But he makes her a deal: if she can help him get back to Kensington, he will promise her a real ruby and all the jewels she could ever want. She accepts and says that first they have to visit her family home. While overhearing a conversation between Rita and her dad, he thinks she has double crossed him and he takes off in her boat. When she catches up to him, he clears up the understanding. Then the pair have to evade Spike, Whitey and the rest of the minions by a chase through the canals of underground London. Angry at Spike and Whitey's constant failures, The Toad sends for his French cousin Le Frog (Jean Reno). Le Frog and his subordinates capture the duo and get back the master cable. And this is right after they go after a waterfall. They manage to escape by chewing the strings off a plastic bag and using the updraft created by the falls to drift up and out over the skyline of London. When they get back home, Roddy gets the jewels he promised Rita and she wants a grand tour of his home. But when she sees his cage, comprehension kicks in and she realizes he's a pet. But when Roddy tries to pass off Sid as his brother, it goes wrong when Rita and Sid know each other. When Rita tries to get Roddy to come along with her, he says he has it all up here. Talking to Sid about half time, this helps him reconnect the Toad's plan. He asks Sid to flush him again so he can rescue the rat city London. With Rita and Roddy working together, they freeze the wall of sewage barreling towards them, saving the entire rat population who has gathered together to see England beat Germany at soccer.
Rita and Roddy make a Jammy Dodger II and they set off in it with Rita's entire family. And in the closing scenes, a newspaper comes up saying Germany won and England lost on penalties, the 2 become boyfriend and girlfriend and Roddy's owner Tabitha comes back with a new pet.. a cat that frightens Sid.
- Hugh Jackman as Roderick "Roddy" St. James - The main protagonist. A lonely pampered pet mouse living in a Kensington apartment with a wealthy English family who is flushed down the toilet by Sid into the sewers.
- Kate Winslet as Rita Malone. The deuteragonist. A street smart scavenger rat and the oldest child of a large family. She is the captain of The Jammy Dodger.
- Ian McKellen as The Toad. The main antagonist. A big, pompous amphibianwanting the entire rat population to be killed off so he can make room for his hundreds of offspring.
- Jean Reno as Le Frog The secondary antagonist. The Toad's French cousin. He masters martial arts and is the leader of a team of hench-frogs.
- Andy Serkis as Spike, one of the Toad's top two hench-rats. Being the Toad's hench-rat is Spike's first job, despite him being only a teenager. He is the smarter of the two.
- Bill Nighy as Whitey, another of the Toad's top two hench-rats. Whitey is an albinorat, once working in a lab and he is Spike's partner. Unlike Spike, Whitey is gentle and less violent, but is also rather slow-witted and dumb.
- Shane Richie as Sid, an over-weight and lazy rat from the sewers. He is an acquaintance of Rita and her family and the one who flushed Roddy down the toilet into the sewers.
Andy Serkis as Spike
Bill Nighy as Whitey
Kate Winslet as Rita
Shane Richie as Sid
Hugh Jackmanas Roddy