〔Abstract〕 Objective To observe the effects of losartan on rat myocardial microvascular endothelial cells and Janus protein tyrosine protein kinase 2/signal transducer and transcriptional activator 3(JAK2/STAT3) signaling pathway, and explore protective mechanism of losartan on diabetes. Methods Rats were divided into a blank control group,(advanced glycation end products) AGEs group, AGEs plus losartan treatment group, and losartan treatment group for advanced glycation end products and losartan intervention. The activity and apoptosis rate of myocardial microvascular endothelial cells in rats were detected by MTT assay and TUNEL assay. The expression levels of related proteins in JAK2/STAT3 signaling pathway were detected by Western blot and RT-PCR. The levels of IL-6 and tumor necrosis factor-β(TNF-β) were detected by ELISA. Results Compared with the blank control group, the viability of myocardial microvascular endothelial cells in the AGEs group was significantly weakened and the apoptotic rate was increased. The expression of related proteins and the expression of related inflammatory factors IL-6 and TNF-β in the JAK2/STAT3 signaling pathway were also significantly elevated(P<0.05). Compared with the AGEs group, the AGEs plus losartan treatment group showed an increase in cell viability and a decrease in apoptotic rate. The expression of related proteins in the JAK2/STAT3 signaling pathway and the expression of related inflammatory factors IL-6 and TNF-β also decreased(P<0.05). There was no significant difference in the expression of related proteins and inflammatory mediators in the losartan group compared with the blank control group(P>0.05). Conclusion Losartan can effectively inhibit the advanced glycation end products through the JAK2/STAT3 signaling pathway, thereby alleviating the damage to myocardial microvascular endothelial cells and protecting them.