The effect of Shakrino, a herbomineral medicine (HMM)) on early diabetic nephropathy in rats was evaluated. The occurrence of early diabetic nephropathy (DN) in rats treated with streptozotocin was revealed by hyperglycemia, depleted liver glycogen, decreased glucose uptake by peripheral tissue, impaired renal function, increased lipid peroxidation and decreased antioxidants in kidney. These changes were associated with increased total urine output, urinary albumin excretion rate, urinary albumin to creatinine ratio, increased relative kidney weight, increased arterial blood pressure, decreased glomerular filtration rate and urinary creatinine in DN rat. HMM treatment (200 and 400mg/kg, p.o., 4 weeks) lowered blood glucose, glycosylated haemoglobin, creatinine, blood urea nitrogen, lipid profiles, serum albumin and total urine output, urinary albumin excretion rate, urinary albumin to creatinine ratio, relative kidney weight, increased urinary creatinine and GFR, and also restored depleted antioxidants, decreased malonolaldehyde formation in kidney of DN rats. Histoarchitecture study showed dense mesangial matrix in glomeruli of DN rats, which were improved by HMM treatment. The protective effect of HMM may be due to the presence of antioxidants like gallic acid, quercetin, β-sitosterol, Jamboline, ellagic acid, gymnemic acid B, α-amyrin and polyphenols.