Abstract: Objective To investigate the effects of resveratrol (Res) on mitochondrial opening and Ca2+-induced Ca2+ release (CICR) from rat liver cell mitochondria mediated by Ca2+. Methods Wistar rat liver cell mitochondria was extracted and Res-induced mitochondrial swelling was assessed spectrophotometrically at 540 nm to examine the permeability transition pore (PTP) opening. The membrane potential changes of Res-treated mitochondia were measured with fluorescence spectrophotometery. Ca2+ uptake and release by the mitochondria was determined by absorbance change of arsenazo Ⅲ at 685-675 nm monitored by dual wavelength spectrophotometry. Results Res promoted Ca2+-mediated PTP opening, and this effect was completely inhibited by CsA and lowered by trifluoperazine. CICR accelerated by Res treatment was completely blocked by ruthenium red and partly by trifluoperazine. Conclusion Res can promote PTP opening by inducing CICR, which may be one of the pathways that Res induces cell apoptosis.