The game, much like the first, was developed for the Sega Genesis and then ported over to the Super NES.

The game ends with Jim saving the Princess, but all three characters eventually turning randomly into cows. The last level of the game is not a typical boss fight, but rather, a race against Psy-Crow through an obstacle course, to get to Princess What's-Her-Name. Yet another, 'The Flyin' King', plays as an isometric shooter, with Jim again on his 'pocket rocket', where a balloon with a bomb must be directed to the end of the level, and defended from enemies, in order to defeat Major Mucus.

Another level, aptly titled 'Inflated Head', has Jim's head inflated much like a balloon, and the player must control Jim as he floats upward, avoiding touching sharp objects which cause him to fall back down to the start of the level, all the while dodging Evil the Cat's attacks. The latter part of the level suddenly switches to a game show/ trivia format, where the player has to answer nonsensical multiple choice questions that commonly have no logically correct answer. In the fourth level, 'The Villi People', the player must guide Jim, defenseless in the disguise of a blind cave salamander, through intestinal passages, while avoiding exploding sheep and hazards embedded in the floor and walls. Other levels stray much farther from this formula.

Additionally, Jim's friend, Snott, travels with him and can be used to stick to and swing from other slimy green surfaces or as a parachute upon jumping. New power-ups include the chip butty, which increases Jim's suit power to 200%. For instance, there are more types of guns to use once found in a level, such as an auto-aiming gun, or the 'Barn Blaster' gun which takes out every enemy visible on the screen. Some levels, such as the opening level, 'Anything but Tangerines', and the game's eighth level, 'Level Ate', play largely the same as the original Earthworm Jim, with the exception of there being a larger variety of moves at the player's disposal. While the majority of levels are still based on run and gun and platform game elements, separate levels incorporate different gameplay elements as well. However, gameplay is much more diverse than in the original game. The purpose of the game is largely the same as it was in the original Earthworm Jim traverse through the levels in order to save Princess What's-Her-Name from Psy-Crow.

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