The objective of this study was to investigate the effect of empagliflozin on the levels of sphingomyelin (SM) and its metabolites, as well as on the activity of aSMase, nSMase, and nCDase in the plasma, kidney, heart, and liver of streptozotocin-induced diabetic and Angiotensin II (Ang II)-induced hypertension rats. Here, SMPD2 is linked to hypertensive disorder.