Insulin induces change of Ca²⁺ content in hepatocytes (Benzeroual K. et al., 1997; Rodrigues M.A. et al., 2008). However, the role of IP3Rs and RyRs in insulin-induced change of Ca²⁺ content in hepatocytes is still unknown. Here we present results of our investigation of insulin effect on on IP3Rs and RyRs in rat permeabilized hepatocytes. Experiments were carried out on humanly killed 4-5 months old Wistar rats (n = 29, weight 0,18-0,2 kg). Isolated liver was perfused with insulin-content solution (external incubation solution contained (in mM): NaCl – 140,0; KCl – 4,7; CaCO3 – 1,3; MgCl2 – 1,0; HEPES – 10,0; glucose – 10,0; pH = 7,4 ; insuline – 0,04 u.) for 10 min at room temperature. Then hepatocytes were isolated by lidase digestion (16 u., 10 min, 37 ToC) and permeabilised by incubating with saponine (0.1 mg/ml, 10 min), which was added to internal incubation solution contained (in mM): NaCl – 20,0; KCl – 120,0; MgCl2 – 1,13; ATP («Sigma», USA) – 2,0, CaCl2 – 1,3, HEPES – 10,0; pH=7,0. Concentration of membrane-bound Ca²⁺ was measured using chlortetracycline. We showed that perfusion of liver with insulin-content solution causes statistically significant increase of membrane-bound Ca²⁺ concentration in permeabilized hepatocytes by 33,57 ± 7,93 % (n = 29, P < 0,001) in comparison to membrane-bound Ca²⁺ concentration after liver perfusion with control solution (no insulin present). This liver perfusion with insulin also changed IP3 and ryanodine effect on membrane-bound Ca²⁺ in hepatocytes. We found that IP3 decreased the membrane-bound Ca²⁺ by 32,00 ± 4,08 % (n = 9, P < 0,05) after perfusion liver by insulin-content solution, but caused an increase of membrane-bound Ca²⁺ content after perfusion with control solution (without insulin). Also ryanodine (5 and 500 nM) decreased concentration of the membrane-bound Ca²⁺ by 16,24 ± 5,21 % (n = 7, P < 0,05) and 26,83 ± 9,45 % (n = 4, P = 0,03), respectively. However, ryanodine (50 nM) did not elicit significant changes in the membrane-bound Ca²⁺ content in permeabilized hepatocytes after perfusion of liver with insulin-content solution. In control experiments ryanodine (5, 50 and 500 nM) caused statistically significant increase of membrane-bound Ca²⁺ content in permeabilized hepatocytes by 22,26 ± 7,54 % (n = 7, P < 0,05), 22,95 ± 7,88 % (n = 9, P < 0,05), 18,85 ± 7,50% (n = 6, P < 0,05), respectively. Thus we conclude: 1) perfusion of liver by insulin-content solution prevented ryanodine’s (50 nM) action and changed on reverse action of ryanodine (5 and 500 nM) and IP3; 2) insulin changes concentration of membrane-bound Ca²⁺. We suppose that perfusion of liver by insulin-content solution increase content Ca²⁺ in intracellular store that is why action of ryanodine and IP3 is opposed to control.