<b><i>Objective:</i></b> To explore the role of platelet-derived growth factor-B (PDGF-B)/platelet-derived growth factor receptor-β (PDGFR-β) signaling in chronic atrial fibrillation (AF). <b><i>Methods:</i></b> Thirty-nine AF patients and 33 patients with sinus rhythm (SR) were enrolled. Twenty canines were randomized into 5 groups: control, sham and AF lasting 1, 2 or 4 weeks. The AF canine models were made by rapid atrial pacing. Rat atrial fibroblasts were treated with PDGF-BB or PDGF-BB + PDGFR inhibitor AG1295, respectively. Gene expression in the right atrial appendage of patients, the left atrium of canines and rat atrial fibroblasts was measured by quantitative real-time PCR and Western blot, respectively. The degree of atrial fibrosis was evaluated by Masson trichrome staining. <b><i>Results:</i></b> The degree of atrial fibrosis and the expression of PDGF-B, PDGFR-β and collagen type I (COL1) in AF patients significantly increased compared to patients with SR. The degree of atrial fibrosis and the expression of PDGF-B and COL1 in canines increased progressively with the increased duration of AF. The expression of PDGFR-β increased progressively 2 weeks after AF. PDGF-BB promoted the proliferation and COL1 secretion of rat atrial fibroblasts. AG1295 attenuated these effects. <b><i>Conclusions:</i></b> Our study suggests that PDGF-B/PDGFR-β signaling, which promotes the proliferation and COL1 secretion of atrial fibroblasts, is an important contributor to atrial fibrosis in AF and may represent a novel target for the intervention of AF.