Objective To observe the protective effect of salvianolic acid A (SAA) on nephropathy and the expression of lipoprotein-associated phospholipase A2 (Lp-PLA2) in Zucker diabetes fatty rats ( ZDF). Methods According to the body weight and blood glucose, 40 male ZDF rats aged 11-12 weeks were randomly divided into five groups (n = 8 per group), namely, a model group, 0. 25, 0. 5, and 1 mg/ kg SAA groups, and a positive (Lp-PLA2 inhibitor at 25 mg/ kg) group. Meanwhile, another eight ZL rats of the same age were used as a normal group. Each drug administration group was given the corresponding drug once a day. Simultaneously, the model group and the normal group were administered normal saline of the same volume daily. After 12 weeks of continuous intervention, the renal microcirculation blood flow of ZDF rats was measured. Lp-PLA2 activity, blood urea nitrogen (BUN), and creatinine (Crea) in serum as well as transferrin (TRF), microalbumin (mALB), and retinol binding protein (RBP) in urine were analyzed. Lp-PLA2 mRNA and protein expression in renal tissue was also examined. Moreover, renal histopathological observation was performed. Results Compared with the control group, the pathological structure of the kidney was clearly changed and renal microcirculation blood flow was significantly decreased in the model group ( P <0. 01), whereas serum Lp-PLA2 activity and BUN levels and urinary TRF, mALB, and RBP were all notably increased ( P <0. 01). Moreover, the expression of Lp-PLA2 mRNA and protein in renal tissues was markedly increased ( P < 0. 01). The changes of these indicators were dramatically ameliorated after the administration of SAA and Lp-PLA2 inhibitor, especially in the groups with SAA at doses of 0. 5 and 1 mg/ kg. Conclusions SAA can improve the symptoms of DN in type 2 diabetic rats, which may be related to the inhibition of Lp-PLA2 activity and mass.