Rosiglitazone is a clinically approved anti-diabetic thiazolidinadione which now is not used anymore due to negative side effects. It acts as proliferator-activated receptor γ (PPARγ) agonist, which is associated with its stimulating effect on brown adipose tissue (BAT) recruitment. The latter effect could be interesting due to the anti-obesity role of BAT. However, the same ability of rosiglitazone to activate PPARγ leads to weight gain. Two novel thiazolidinadiones, MSDC-0602 and MSDC-0160, have been suggested as potent anti-diabetic drugs acting by a mechanism independent of PPARs and potentially lacking the negative side effect on weight gain (1). In this work we studied in vivo effects in mice of these two novel agents in comparison to the effect of rosiglitazone. Mice were kept in thermoneutrality and on high fat diet to stimulate obesity. Drugs were administered with food (rodent diet with 45 kcal% of fat and 300 ppm of Rosiglitazone, MSDC-0160 or MSDC-0602, ad libitum). We confirmed that rosiglitazone results in slight body weight gain in comparison to control mice. The same effect was shown for MSDC-0160. However, another drug, MSDC-0602, actually decreased body weight and was thus considered as the most promising. Weight of inguinal white adipose tissue (iWAT) was consistent with body weight: mice treated with rosiglitazone or MSDC-0160 had larger iWAT depot in comparison to control mice, whereas MSDC-0602 decreased the weight of the tissue. We also measured effects of the drugs on expression of UCP1 and mitochondrial respiratory chain proteins in interscapular brown (iBAT) and iWAT. Examination of iBAT showed that none of the drugs increased the amount of UCP1 per mg of tissue protein. However due to the fact that rosiglitazone and MSDC-0160 resulted in brown adipose tissue recruitment, total UCP1 amount in the tissue was doubled. However, neither rosiglitazone nor MSDC-0160 resulted in significant increase of total amount of respiratory chain proteins in tissue. No effect of the most promising drug MSDC-0602 on proteins levels in iBAT was observed. All drugs had prominent effects on iWAT. Levels of UCP1 and respiratory chain proteins were significantly increased with all drugs, although rosiglitazone had more profound effect. However, the browning of iWAT in treated mice did not increase UCP1 amount to more than 5 % of the untreated level of iBAT. Thus, considering the absence of effect on body weight gain and significant increase of brite adipose tissue in MSDC-0602 treated mice, the novel tiazolidinedione, MSDC-0602 could be suggested as a potential anti-diabetic and anti-obesity drug.