Abstract: AIM:To investigate the effect of baicalin (BC) on endoplasmic reticulum stress (ERS) tunicamycin-induced cardiomyocyte injury. METHODS: Tunicamycin (Tm) was used to establish the model of endoplasmic reticulum stress in cultured neonatal rat cardiomyocytes, which were divided into four groups: control group, BC group, Tm group and BC+Tm group. MTT assay was used to detect cell viability, LDH release and TUNEL assay were applied to determine cell damage, and Western blot was used to detect protein expressions of C/EBP-homologous protein (CHOP). RESULTS: Tm damaged the myocardial cell in a time-dependent manner, which showed significant differences from those in the normal group at all timepoints (P<0.05). Tm significantly increased the CHOP expression of ERS and apoptosis level. Presence of BC (50 μmol/L) markedly improved cell viability against Tm-induced myocardial cell injury when compared with Tm group (P<0.05). BC significantly lowered the expression of CHOP and apoptosis, which inhibited ERS Tm-induced injury in cultured neonatal rat cardiomyocytes (P<0.05). CONCLUSION: Baicalin protects cardiomyocytes against Tm-induced injury through attenuation of ERS.