In this study, the effects of $Ca^{2+}$ and cyclic adenosine monophosphate (cAMP) on microsomal triglyceride (TG) transfer protein (MTP) activity were investigated in rat liver. MTP activity was high when liver contained low levels of cAMP, which was induced by administration of glucose, or high levels of total $Ca^{2+}$ and TG. However, MTP activity increased by high levels of $Ca^{2+}$ and TG was reduced in a dose-dependent manner by treatment with dibutyryl-cAMP (db-cAMP), a cAMP analogue. Conversely, when homogenates of liver from normal rats, with low levels of total $Ca^{2+}$ and high levels of cAMP, were incubated with thapsigargin, a $Ca^{2+}$-inducer, MTP activity was increased in a dose-dependent manner compared to control. Therefore, our results suggest that high levels of $Ca^{2+}$ cause hypertriglyceridemia through the elevation of MTP activity, as opposed to high levels of cAMP, which suppress MTP activity and inhibit hypertriglyceridemia.