A series of thiazolidin-4-one derivatives possessing ester were synthesized under microwave irradiation, and then the corresponding products with hydrophilic groups, like carboxyl and hydroxyl groups, were obtained after hydrolysis reaction or reduction reaction. The compounds were evaluated for their human immunodeficiency virus (HIV) reverse transcriptases inhibitory activities in vitro HIV-RT kit assay (colorimetric method). The results showed that some of the compounds, such as 8a, 8b, 9a, 9b and 14c, could effectively inhibit RT activity. Among them, compounds 8a and 9a where ethyl group existed at 5-position on N-3 pyrimidine ring were the best ones with the IC 50 values of 3.02 and 3.06 μmol•L -1 , respectively. Structure activity relationship analysis of these analogues suggested that the introduction of hydrophilic groups had little effect on their anti-HIV-RT activity and the N-3 pyrimidine moiety on thiazolidin-4-one ring should be more favorable to the anti-HIV activity than the C-2 phenyl group.