What is the main theme of the story?

I would consider acceptance as the main theme. The overriding theme is manifested in the way that it is a given that Stuart is a mouse who is capable of living like a human being. The Littles begin from a point of unquestioned validity that Stuart is a mouse and so this fact never becomes the central issue of the narrative. From this point of unquestioned acceptance by a parent, the narrative can then continue to allow Stuart’s quite obvious divergence from the norm to be addressed by others, thus making acceptance of those who are different the primal driving thematic force behind that narrative.