It is known that Cd²⁺ activates mitochondrial (Mit) swelling following by opening of the permeability transition pore (PTP), fast Ca²⁺ release from the Mit matrix as well as the other pathological processes which may result in the cell damage and death. However the mechanisms contributing to the Mit swelling remain elusive. The aim of this study was to find out the kinetics and molecular mechanisms of the Cd²⁺-induced Mit swelling. The experiments were performed on the Mit isolated from adult Wistar rats liver. The rats were anaesthetized by inhalation narcosis with diethyl ether. Mit were obtained by differential centrifugation (1). Mit swelling was measured spectrophotometrically and analyzed by three parameters: i) maximal rate of the process; ii) process lag-time; iii) peak amplitude of the response (2). We showed that increase of extra-Mit concentration of Cd²⁺ (1-50 μM) caused decrease in the lag-time and the peak amplitude of the Cd²⁺-induced Mit swelling, but increased the rate of the process. The dependence of the rate of Mit swelling on added Cd²⁺ was sigmoid (EC₅₀ = 7,276±1,750 μM, V_max = 1,084±0,195 A₅₄₀/min×mg protein; n = 5). We also found that incubation of Mit with PTP inhibitor − cyclosporin A (10 μM, 1 min) did not prevent the Cd²⁺-induced Mit swelling. In particular, the rate of the process stimulated by 15 and 50 µM of Cd²⁺ was 61±5 % (n = 6; p = 0,000) and 71±4 % (n = 6; p = 0,000); lag-time − 193±16 % (n = 6; p = 0,000) and 132±8 % (n = 6; p = 0,001); peak amplitude − 102±4 % (n = 6; p = 0,747) and 108±6 % (n = 6; p =0,403) respectively compare to control. Incubation of Mit with the chelator of SH-groups − dithiothreitol (1 mM, 1 min) completely eliminated the Cd²⁺ (15, 50 µM)-induced Mit swelling. In addition we showed that incubation of Mit with modulator of COOH-groups − 2-ethoxy-1-ethoxycarbonyl-1,2-dihydroquinoline (1 mM, 1 min) slightly potentiated the Cd²⁺-induced Mit swelling. In particular, the rate of the process stimulated by 15 and 50 µM of Cd²⁺ was 114±10 % (n = 5; p =0,033) and 125±9 % (n = 5; p =0,013); lag-time − 74±9 % (n = 5; p =0,010) and 85±10 % (n = 5; p =0,170); peak amplitude − 108±5% (n = 5; p =0,031) and 105±7 % (n = 5; p =0,356) respectively compare to control. Thus, our results detailed the main kinetic parameters of the Cd²⁺-induced Mit swelling in hepatocytes and strongly suggested that this process is not mediated by the opening of PTP, however is significantly regulated by SH- and COOH-groups of the inner Mit membrane.