The pathogenesis of diabetic nephropathy, mainly characterized by macroalbuminuria, is still poorly understood, but it is reported that transforming growth factor-β (TGF-β) plays a key role. In vitro evidence suggests that administration of oxidized LDL (ox-LDL) can lead to upregulation of TGF-β by human glomerular mesangial cells. This study aimed to evaluate the association between macroalbuminuria, ox-LDL, and TGF-β in diabetic patients. A total of 77 type 2 diabetic patients with macroalbuminuria (albumin excretion rate: AER ≥ 300 mg/24 h) and 66 patients with normoalbuminuria (AER ≤ 30 mg/24 h) were recruited. Fasting blood samples were obtained and serum levels of ox-LDL and TGF-β were determined. Ox-LDL and TGF-β were significantly higher in patients with macroalbuminuria than in those with normoalbuminuria (98.93 ± 3.99 vs. 72.45 ± 2.48 U/l; P < 0.001 and 6.46 ± 0.74 vs. 2.49 ± 0.39 ng/ml; P < 0.001, respectively). In patients with macroalbuminuria, there was a significant correlation between Ox-LDL and TGF-β (r = 0.376; P < 0.01). AER was significantly correlated to ox-LDL (r = 0.302; P < 0.05) and TGF-β (r = 0.306; P < 0.05) in macroalbuminuric patients. This association remained significant after adjustment for potential confounders. Adjustment for TGF-β (ox-LDL), attenuated the association of ox-LDL (TGF-β) with AER. In conclusion, this study demonstrated the association of TGF-β and ox-LDL with albuminuria in macroalbuminuric type 2 diabetic patients, and suggested that this relationship is highly mediated through the correlation between TGF-β and ox-LDL.