Aim To investigate the effects of acupuncture combined with Tangke apozem on transforming growth factor-β1 (TGF-β1), matrix metalloproteinase-9 (MMP-9) and connective tissue growth factor (CTGF) in diabetic nephropathy rats. Methods 54 SPF SD male rats were selected, and 8 of them were randomly selected as control group. The remaining rats were subjected to diabetic nephropathy (DN) model replication, one-time rat tail vein injection of streptozotocin. Rats were randomly divided into model group, irbesartan group, acupuncture combined with Tangke apozem group (acupuncture combined with traditional Chinese medicine group), Tangke apozem treatment group (Chinese medicine group) and acupuncture group. Observe the general condition of the rats, and measure body weight, blood sugar, kidney weight/body weight, 24-hour urine protein, blood urea nitrogen (BUN), serum creatinine (SCr), triglyceride (TG) and total cholesterol (TC); HE staining, Masson staining and glycogen staining (PAS) were used to observe changes in renal tissue morphology; The protein expression levels of TGF-β1, MMP-9, collagen Ⅰ, CTGF, and TIMP-1 in kidney tissues were detected by Western blot method. Results Compared with the model group, the weight, kidney weight/body weight ratio, 24 h urine protein, BUN, SCr, TG, TC of the acupuncture combined with traditional Chinese medicine group, Chinese medicine group and irbesartan group were significantly improved, and the combination of needle and medicine was more remarkable. The acupuncture group slightly improved. The expression levels of TGF-β1 and CTGF protein were significantly decreased. The expression of TIMP-1 was down-regulated by adjusting the protein expression of MMP-9, and the hydrolysis of Collafen Ⅰ was accelerated. The expression of TGF-β1, CTGF and TIMP-1 in the acupuncture combined with traditional Chinese medicine group was significantly lower than that in the traditional Chinese medicine or irbesartan group, and the expression of MMP-9 was increased. The acupuncture combined with traditional Chinese medicine group was more effective than the Chinese medicine group and the Western medicine group. Conclusions Acupuncture combined with Tangke apozem has obvious therapeutic effect compared with traditional Chinese medicine group. It can effectively regulate the expression of TGF-β1, MMP-9 and CTGF, reduce glomerular sclerosis, reduce proteinuria and prevent renal function, and protect DN lesions. The progress has been delayed.