The hemodynamic effect of diltiazem (DTZ) in several different rodent models following repeated subcutaneous injections were compared.  Male Sprague Dawley (SD), spontaneously hypertensive rat (SHR), and Wistar Koyoto (WKY) rats (Charles River Laboratories, n = 6 - 10 per group) weighing between 300 - 450 g were used. Each rat received either saline (control) or 5 mg/kg of  DTZ subcutaneously twice daily for 5 doses. Hemodynamic measurements were recorded from the carotid artery continuously for each animal before and following treatment for up to 6 h.  The average SBP and DBP in the control groups were 126 ± 20 and 101 ± 22 mmHg in the SD rats, 168 ± 27 and 130 ± 11 mmHg in the SHR, and 135 ± 17 and 109 ± 15 in the WKY rats, respectively (p < 0.05). The HR was higher in the SD rats, followed by the SHR and then the WKY rats, although only the differences between the SD and WKY rats, and those between the SHR and WKY rats were statistically significant (p < 0.05).  The study reports for the first time that DTZ decreased the SBP and DBP significantly in SHR, WKY and SD rats. DTZ also decreased HR in the rat models, but the effect was not statistically significant (p > 0.05). The BP responses to DTZ were significantly greater in the SHR than in the SD rats, albeit that the hemodynamic effects were qualitatively similar. The results also suggest that the WKY rat may be a more suitable control model as both HR and BP are significantly lower in the WKY rats than the SHR.