In the present study, we have shown that the administration of CB1 receptor antagonist, rimonabant significantly improved hepatic steatosis and inflammation, which was accompanied by an increase in the Nrf2 and its downstream effectors such as NQO1, HO-1, GSAT, and TXNRD1 expression, major regulators of a cellular defense system against oxidative stress, as well as AMPK phosphorylation in severely uncontrolled diabetic OLETF rats. This evidence concerns the gene NFE2L2 and Hepatic steatosis.