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Introduction and Objectives Pulmonary arterial hypertension (PAH) is a fatal disease characterised by progressive vascular remodelling and metabolic dysregulation. Key hallmarks of PAH metabolism include enhanced glycolysis, increased glutamine utilization, decreased fatty acid oxidation and impaired TCA cycle. However, the detailed profile of these metabolic shifts remains incompletely characterised during PAH development. Here we explored the whole body and tissue specific metabolic changes in the monocrotaline (MCT)-induced PAH rat model.Methods MCT (60 mg/kg, 4 weeks)-induced PAH rat model was used to investigate the whole body metabolic profile for healthy baseline and 1–4 weeks after MCT injection using the comprehensive lab animal monitoring system (CLAMS). Tissue specific metabolism, including liver and right ventricular (RV), was assessed using high-resolution respirometry (Oroboros) at weeks 3 and 4. PAH phenotypes were evaluated by echocardiography and Fulton’s index.Results As MCT-induced PAH developed, both male and female rats demonstrated decreased oxygen consumption (VO2) and carbon dioxide production (VCO2) in light and dark cycles. From week 1 to week 3, both male and female showed an increased respiratory exchange ratio (RER), suggesting a metabolic shift preference for carbohydrate metabolism versus fat. Female maintained elevated RER levels through week 4. Male RER increased through week1–3 with an initial drop from baseline but exhibited a significant reduction at week 4. Oroboros data indicated that MCT significantly reduced RV mitochondrial function, indicated by decreased mitochondrial oxidative phosphorylation, complex I, II activity and electron-transfer-pathway (ET) capacity at weeks 3 and 4. Liver mitochondrial respiration, including oxidative phosphorylation, complex I, II and ET capacity, was significantly increased at the same period. At week 4, female exhibited higher RV mitochondrial respiration, consumed more food and produced more heat than males at week 4. ECHO and RV hypertrophy indicated more severe PAH phenotypes in males than females at weeks 3 and 4.Conclusion This study described the rat’s whole body and tissue specific metabolic profile during the MCT-induced PAH development for the first time. Our results support the metabolic difference between the male and female in PAH. This pattern may underlie observed differences in disease severity and therapeutic response in different sexes.