Abstract: Objective To investigate the effect of fluoxetine on neurite growth inhibitor (Nogo) expession and collagen production of cardiac tissue in rats with right heart failure and pulmonary hypertension. Methods Thirty one male SD rats were randomly divided into the treatment group，right heart failure group and normal control group. The rats in the treatment group and right heart failure group received intrapertioneal injection of monocrotaline (MCT, 60 mg/kg) to induce pulmonary hypertension and right heart failure. After 21 days, the rats in treatment group were given fluoxetine of 10 mg/（kg·d） by gavage per day for 21 days, the rats in the other two groups were given saline. HE staining was used to observe the pulmonary artery and right ventricular myocardial tissue in rats. The collagen formation in right ventricular myocardium was observed by Masson staining. The expressions of Nogo-A，Nogo-B, typeⅠcollagen and type Ⅲ collagen mRNA in myocardium were measured by real-time fluorescence quantitative PCR, while the semi quantitative measurement of Nogo protein level was detected by Western blot. Results After the intervention of fluoxetine, pulmonary artery stenosis was significantly reduced, myocardial tissue lesion decreased, collagen synthesis decreased in right ventricular myocardium. RT-PCR showed that mRNA of Nogo-A decreased, and mRNA of Nogo-B increased (P<0.05). Western blot showed that the expression of Nogo-A protein decreased, while Nogo-B1 protein expression increased (P<0.05),Nogo-B2 expression was not significantly changed (P>0.05). Conclusion Nogo may affect the collagen synthesis in right heart failure, and partly involved in myocardial fibrosis.