Objective To investigate the effect of Huangqi Shengmai Yin (HSY) on myocardial fibrosis in rats with acute myocardial infarction (AMI) by adjusting P2X purinoceptor 7 (P2X7R)/NOD-like receptor protein 3 (NLRP3) pathway.    Methods Sixty rats were divied into a sham operation group and model group(5 groups), with 10 rats in each group. The AMI rat model was constructed by ligating the left anterior descending branch and randomly grouped into AMI group, the HSY-low group (intragastric administration of 1.6 ml/kg HSY), the HSY group (intragastric administration of 6.2 ml/kg HSY), the compound miltiorhiza group (intragastric administration of 300 mg/kg), and the HSY-high+P2X7R agonist-ATP group (intragastric administration of 6.2 ml/kg HSY, and tail vein administration of 10 mmol/L ATP). After the intervention, cardiac function, myocardial injury and inflammatory factor markers were detected. The tissue sections were prepared to examine pathological changes, myocardial fibrosis, type Ⅰ and type Ⅲ collagen (COL1A1, COL3A1). Western blotting was performed to detecte the protein expression of P2X7R, NLRP3, tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), and the expression of activated Caspase-1.  Results Compared with the sham surgery group, the AMI group showed an increase in the left ventricular end diastolic diameter (LVEDD), the coatent of brain natriuretic peptide (BNP) and cardiac troponin Ⅰ (cTnⅠ), fibrosis volume fraction, the positive expression of COL1A1, COL3A1, TNF-α, IL-1β, P2X7R, NLRP3, and activated Caspase-1 proteins (P<0.05), and a decrease in left ventricular ejection fraction (LVEF) (P<0.05). The HSY-low group, HSY-high groups, and compound miltiorhiza group showed a decrease in LVEDD, the content of BNP and cTnⅠ, fibrosis volume fraction, the positive expression of COL1A1 and COL3A1, TNF-α, IL-1β, P2X7R, NLRP3, and activated Caspase-1 proteins (P<0.05), and an increase in LVEF than these in the AMI group (P<0.05). The HSY-high+ATP group showed an increase in LVEDD, the content of BNP, cTnⅠ, fibrosis volume fraction, the positive expression of COL1A1 and COL3A1, TNF-α, IL-1β, P2X7R, NLRP3, and activated Caspase-1 proteins (P<0.05), and a decrease in LVEF than those in the HSY-high group (P<0.05).   Conclusion HSY inhibits P2X7R/NLRP3 pathway to alleviate myocardial fibrosis in AMI rats.