OBJECTIVE: To investigate whether pterostilbene could activate eNOS and reduce neutrophil accumulation and tumor necrosis factor α (TNF-α) induction in an ischemia/ reperfusion injured rat heart model. STUDY DESIGN: Rats were randomly exposed to sham operation, myocardial ischemia and reperfusion (MI/R), MI/R+pterostilbene, or MI/R+pterostilbene+L-NAME. Myocardial infarct size, apoptosis, TLR4 expression, NF-κB expression, myeloperoxidase (MPO) level, and TNF-α level were detected. RESULTS: The results demonstrated that after MI/R, the expressions of myocardial TLR4, NF-κB, and caspase-3 increased significantly in the ischemia area. Compared with MI/R, pterostilbene significantly attenuated the expressions of TLR4, NF-κB, and caspase-3. In addition, it also reduced MPO levels, both serum and myocardial TNF-α production, myocardial infarct sizes (INF/ AAR%), and myocardial apoptosis induced by MI/R. All the effects of pterostilbene were abolished by L-NAME, a nitric oxide synthase inhibitor. CONCLUSION: These data provide evidence that pterostilbene inhibits inflammation and apoptosis in the rat heart subjected to MI/R via eNOS activation. © Science Printers and Publishers, Inc.