Diabetic nephropathy is one of the most prevalent chronic complications of Diabetes mellitus, but its pathogenesis remains elusive. This study was designed to determine the role of tristetraprolin (TTP), inflammatory cytokines and microRNAs (miRNAs) in DN. The blood and urine samples were obtained from 32 patients with DN, 33 patients with type 2 DM, and 35 normal healthy subjects as controls. Renal tissue samples were also obtained from 10 DN patients and 10 normal controls. The miRNA microarray analyses were performed in pooled plasma and urine sediment samples of eight DN patients and eight age- and sex-matched health control subjects and three paired renal tissues from patients with DN and normal controls. Conditionally immortalized mouse podocytes (MPC5) were used a cell model. The expressions of TTP and cytokines in patient samples and cultured cells were determined by qRT-PCR and Western blotting or ELISA. Our results indicated that miRNA-29c directly targeted TTP and promoted inflammatory response under hyperglycemic conditions. Overexpression of miRNA-29c in podocytes resulted in an increase in inflammatory cytokines and inhibition of miRNA-29c by using its inhibitor reduced the inflammatory cytokines in podocytes. Finally, miRNA-29c promoted the progression of DN by targeting TTP, providing a target for a therapeutic intervention of DN.