Squeak's herculean friend Biff visits Garfield's house and turns it into a mouse gym. Meanwhile, Squeak, who is accidentally inside Jon's suitcase, tries to return home.
Harry, Lucky, and Myron check out the fish outside a pet shop. Lucky tells the other two that he is craving a mouse. Harry remarks that he hasn't eaten any mice in a long time, while Myron notes that he has never eaten mice in his life. As they walk away from the pet shop, Myron asks why Garfield does not eat mice. He is told that Garfield has befriended the mice, as well as being put off by their taste.
At the Arbuckle house, the mice are enjoying their time in the living room, as Garfield gives them pieces of cheese. Squeak then tells his friends to save a piece of cheese for his old classmate Biff, who will be visiting the house. The mice hide when Jon approaches the living room. Jon informs Garfield that he'll be out of town for a week. Jon gets a snack bag for the trip, unaware that Squeak is in said bag, and put it in his suitcase. As the rest of the mice come out of hiding, Biff comes in and inquires about Squeak. Garfield gets most of the mice to hide again when Jon come back into the room. Since Biff is unwilling to hide, Garfield sits on him as Jon returns.
Before leaving, Jon tells Garfield that he expects the house to be kept mouse-free. After Jon leaves, Biff, still under the fat cat, throws Garfield off, and the rest of the mice come out. Disappointed with the other mice being out of shape, Biff makes them exercise. Garfield tells Odie to search the house to find Squeak. After an airplane trip, Squeak finally gets out of the suitcase while Jon stops at a hotel in another part of the world. A mouse tells him that they are in Mexico, prompting Squeak to return home. At a post office, Squeak writes Jon's address on a postage box and gets delivered in the box.
A week later, the living room of Jon's house is filled with mice lifting cheese barbells, doing jumping jacks, pushups, or running laps. Garfield tells Odie that Squeak is still missing, and Jon will soon be returning home. Garfield tries to get Biff to leave, but Biff has no interest in doing so until Squeak returns.
From outside, Harry, Lucky, and Myron notice that the inside of Garfield's house is full of mice. Myron, curious about how mice taste, goes inside first through the kitchen doggie door. He captures two mice, Irv and Emily, and tosses them to Harry and Lucky, as the two mice scream for help. Biff notices the three cats and thinks that one of them ate Squeak. He then proceeds to rough them up, freeing Irv and Emily during the mayhem.
Meanwhile, Garfield finds Herman Post at the door with the box containing Squeak. After Herman leaves (due to hearing loud noises from inside the house), Garfield opens the box and finds Squeak. After Biff throws out the other cats, he is relieved to see Squeak alive and well. Jon then returns home, satisfied to see the house without any mice. After Jon leaves, Biff suggests Garfield should exercise. Garfield does so until he slips on a cheese barbell.