Aim To investigate the effect of microRNA-146b (miR-146b) on the expression of p38 Mitogen-Activated protein kinase(p38MAPK) in human acute monocytic leukemia cell line(THP-1). Methods Cell model was established by angiotensinⅡ(AngⅡ)stimulation. Pre-miR-146b-3p or anti-miR-146b-3p were transfected by lentivirus and the expression of p38MAPK and COX2 were detected. p38MAPK siRNA was transfected and the expression of p38MAPK and cyclooxygenase(COX2) in THP-1 cells were detected. Results The expression of p38MAPK and COX2 was increased in THP-1 cells stimulated by AngⅡand pre-miR-146b-3p could amplify the effect. p38MAPK siRNA decreased the ability of pre-miR-146b-3p to increase levels p38MAPK and COX2. The difference was statistically significant (P<0.01). Conclusion miR-146b may regulate COX2 expression by p38MAPK in AngⅡstimulated THP-1 cells, and may play an important role in the diagnosis and treatment of cardiovascular diseases.