BACKGROUND: Our previous study showed that during in vitro experiments changes in calcium concentration were associated with apoptosis. We presumed that the calcium ion might play a role as intermediate messenger for apoptosis-related genes. No such evidence has been reported in the literature. Here, we investigate the effect of calcium ionophore A23187 on the apoptosis of rat hepatic stellate cells (HSCs) stimulated by transforming growth factor-β(1) (TGF-β(1)) to explore the mechanism of apoptosis through the endoplasmic reticulum stress pathway. METHODS: The apoptotic rate was determined using flow cytometry. The changes in Ca(2+) level in HSCs were examined with laser confocal microscopy. The expressions of caspase-12 GRP78 and caspase-9 were assayed via western blot. RESULTS: The respective apoptosis rates for the blank group, the TGF-β(1) group and the TGF-β(1)?+?low, medium and high dose calcium ionophore A23187 groups were 3.40?±?0.10%, 1.76?±?0.12%, 5.86?±?0.31%, 11.20?±?0.48% and 15.08?±?0.75%, with significant differences between the groups (p?