Aim To investigate the protective effect and mechanism of salvianolic acid B (SalB) on oxidized low density lipoprotein (ox-LDL)-induced foam cell formation in atherosclerosis. Methods Bone marrow-derived macrophages (BMDM) were extracted from mice, and cells were induced with 50 mg/L ox-LDL. The Piezo1 channel agonist Yoda1 was added to observe the correlation with Piezo1. The drug group was treated with different concentrations of SalB. Results Foam cell formation was significantly increased in Yoda1+ox-LDL group(P＜0.05). Compared with Yoda1+ox-LDL group, foam cell formation was significantly inhibited in SalB group (P＜0.05). Compared with normal control group, the protein expressions of inflammatory factors were increased in ox-LDL group, and they were more obvious in Yoda1+ox-LDL group. The protein expression levels of inflammatory factors were significantly decreased in SalB group(P＜0.05). In addition, the translocation of YAP protein into the nucleus was obvious in ox-LDL group, while it was more obvious in Yoda1+ox-LDL group, and the difference was significant (P＜0.05). The translocation of YAP protein into the nucleus was significantly reduced in SalB group. The expressions of phosphorylated P38, ERK1/2 and JNK proteins were increased in ox-LDL group and Yoda1+ox-LDL group, while they were significantly decreased in SalB group, and the difference was statistically significant (P＜0.05). Conclusion SalB inhibits foam cell formation and the protein expression levels of inflammatory factors induced by ox-LDL and Yoda1, thereby delaying the formation of atherosclerotic plaques. The mechanism may be that salvianolic acid B mediate Piezo1 to regulate MAPK/YAP axis.