Data here obtained confirm the connection between pioglitazone and AnxA1 on treatment of experimental colitis, evidencing the inhibition of AnxA1 cleaving into its inactive form as a mechanism of action of pioglitazone; therefore, we suggest AnxA1 is as a key player required for the anti-inflammatory actions of pioglitazone and thus possibly other PPARγ ligands. This evidence concerns the gene PPARG and colitis.