Objective To investigate the role of HDAC9 in regulating PDE4b in cardiac hypertrohpy. Methods 8-week old male c57 mice were treated with TAC surgery, Sham for mice of control group. 6 weeks after TAC and Sham surgery, heart samples were collected. Cardiac general morphology was evaluated by H&E staining, heart weight/ body weight ratio was calculated. Immunostaining was used for detecting activity of HDACs. Q-PCR was employed to determine expression levels of BNP, PDE4b, HDAC4, HADC5 and HDAC9. The protein levels of PDE4b and HDAC9 were detected by Western blot. ChIP-q-PCR was employed to analyze the binding status of HDAC9 with the promoter region of PDE4b. Results Heart ventricle and septum were significant hypertrophied. HW/BW was increased 4 weeks after TAC surgery (P＜0.05). The expression levels of MYH7 and HDAC9 were increased compared with the controls (P＜0.05). Total HDACs activity was enhanced in failure hearts (P＜0.05). PDE4b levels reduced in mice of TAC surgery group (P＜0.05). Binding affinity of HDAC9 with the promoter of PDE4b was reduced significantly (P＜0.05). Conclusion HDAC9 regulating PDE4b low expression may cause cardiac hypertrophy remodeling.