Background: Aggravating effect of estrogen replacement therapy on glomerular injury associated with an elevation of growth hormone (GH) levels has been reported. Therefore, in the present study, to clarify an association between GH elevation and the aggravating effect of estrogen on glomerular injury, we investigated the effect of somatostatin, an inhibitor of GH secretion, on glomerular injury in estrogen-treated hypercholesterolemic female Imai rats. Method: Control female rats were assigned to group 1 (Cont, n = 10). Group 2 (Cont-E, n = 10) received estrogen, and groups 3 (Cont-E-LS, n = 10) and 4 (Cont-E-HS) received estrogen and either a low dose of somatostatin analogue or a high dose of somatostatin analogue. Body weight, urinary protein, serum albumin, total cholesterol, triglycerides, blood urea nitrogen and serum creatinine were investigated every 4 weeks from 10 weeks through 30 weeks of age. At 30 weeks of age, rats were studied morphologically. Results: Estrogen administration resulted in an increase in urinary protein excretion rates and serum total cholesterol levels, and aggravated glomerular injury associated with an increase in GH. In contrast, somatostatin treatment reduced both urinary protein excretion rates and total cholesterol levels and attenuated glomerular injury to levels close to those of controls associated with a reduction of GH levels. Conclusion: The results suggest that increased GH levels may contribute to an enhancing effect of estrogen administration on glomerular injury.