Abstract: OBJECTIVE To investigate the effect of PM2.5 exposure on myocardial ischemia-reperfusion injury（MIRI）in rats and the protective effect and mechanism of sofren injection from myocardial endoplasmic reticulum stress and apoptosis. METHODS Particulate matter of air was collected and suspended in saline. 48 SPF Sprague-Dawley male rats were randomly divided into 4 group：①Sham-operated group（n=12）; ②I/R group（n=12）；③PM+I/R group（n=12）；④PM2.5+I/R+DZ group. Sham-operated group， I/R group were gave the same volume of PM2.5 normal saline through intratracheal instillation before surgery， once every 48 h for 3 times， Sham-operated group， I/R group and PM2.5+I/R group were injected the same volume of normal saline for 3 days. At the end of the experiment， echocardiography was detected after anesthesia. The expression of endoplasmic reticulum stress-related protein GRP-78， XBP1and CHOP were detected by western blot and qPCR ; TUNEL was used to detect the rate of cardiomyocyte apoptosis. RESULTS Compared with I/R group， left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) in PM2.5+I/R group decreased significantly， myocardial apoptosis rate increased significantly，GRP-78， CHOP transcription and protein levels and XBP1s/XBP1u increased significantly(P<0.01). Compared with PM2.5+I/R treatment group， LVEF and LVFS of DZ group increased significantly， myocardial apoptosis rate decreased， GRP-78，CHOP expression in transcription and protein levels decreased significantly(P<0.01)，XBP1s/XBP1u decreased significantly(P<0.05). CONCLUSION Exposure to PM2.5 can aggravate MIRI. Treatment of sofren injection attenuates MIRI after PM2.5 exposure. The mechanism may be related to inhibition of endoplasmic reticulum stress and apoptosis.