The prevalence of diabetes mellitus (DM) is increasing at an alarming rate throughout the world. Cardiovascular disease is the major cause of morbidity and mortality in diabetic patients and hearts of diabetic patients are frequently in a compromised electromechanical condition. Hyperglycemia is a hallmark sign of DM and pre-diabetes. The majority of currently available glucose-lowering agents work via insulin-dependent mechanisms. The search for newer treatments, with novel therapeutic targets, has led to the development of alternative insulin-independent treatment strategies and one of these is a class of drugs that inhibit the sodium-glucose co-transporter (SGLT). Inhibition of this transporter promotes increased renal glucose excretion, and therefore calorie loss, improved glycemic control and weight loss. The effects of dapagliflozin (DAPAG), a selective SGLT-2 inhibitor, on ventricular myocyte shortening and intracellular Ca2+ transport have been investigated in streptozotocin (STZ) – induced diabetic rats. Experiments were performed at 35-36 °C in ventricular myocytes from diabetic rats after 2 months of STZ treatment and age-matched controls. Myocyte shortening, intracellular Ca2+ and L-type Ca2+ current were measured by video edge detection, by fluorescence photometry and by whole-cell patch clamp techniques, respectively before and after 5 min application of DAPAG (10-6 M). The general characteristics of diabetic rats compared to controls included significantly (p<0.05) increased heart weight/bodyweight ratio and non-fasting blood glucose. Short-term exposure (5 min) of DAPAG (10-6 M) significantly reduced the amplitude of shortening in myocytes from diabetic/DAPAG (5.23±0.33%) vs. diabetic (6.70±0.36%) and modestly reduced shortening in control/DAPAG (6.07±0.48%) vs. control (7.76±0.54%). Amplitude of the Ca2+ transient was significantly reduced in myocytes from diabetic/DAPAG (0.17±0.02 fura-2 ratio units – RU) vs. diabetic (0.25±0.02 RU) and modestly reduced in control/DAPAG (0.19±0.01 RU) vs. control (0.21±0.01 RU) rats. Amplitude of L-type Ca2+ current was significantly reduced in myocytes from diabetic compared to control rats across a range of test potentials and was additionally modestly reduced by DAPAG. Acute application of DAPAG reduced the amplitude of shortening in ventricular myocytes from control and diabetic rats. Alterations in mechanism(s) of Ca2+ transport may partly underlie the negative inotropic effects of DAPAG in myocytes from control and streptozotocin-induced diabetic rat heart.