Background: Pulmonary arterial hypertension (PAH) is associated with mutations of bone morphogenetic protein receptor II (BMPR2) and BMPR2 expression decreases with the development of experimental PAH. Decreased BMPR2 expression and impaired intracellular BMP signaling in PA smooth muscle cells (PASMC) suppresses apoptosis and promotes proliferation thereby contributing to the pathogenesis of PAH. We hypothesized that overexpression of BMPR2 in resistance PAs would ameliorate established monocrotaline PAH. Methods: Human BMPR2 was inserted into a serotype 5 adenovirus with a green fluorescent protein reporter (GFP). Dose-dependent, transgene expression was confirmed in PASMC cells using fluorescence microscopy, qRT-PCR and immunoblots. PAH was induced by injecting Sprague Dawley rats with monocrotaline (60mg/kg ip) or saline. On day 14 post MCT monocrotaline rats received 5X10⁹ pfu of either Ad-hBMPR2 or Ad-GFP. Transgene expression was confirmed by fluorescence microscopy, quantitative RT-PCR of whole lung samples, and laser capture micro-dissected resistance PAs. Invasive hemodynamic and echocardiographic endpoints of pulmonary hypertension were assessed on day 24. Results: Endogenous BMPR2 mRNA levels were greatest in resistance PAs and expression declined with MCT-PAH. Despite robust hBMPR2 expression in all lung lobes and within resistance PAs of treated rats, hBMPR2 did not lower mean PA pressure, pulmonary vascular resistance index, RV hypertrophy, or remodeling of resistance PAs. Conclusion: Nebulized intratracheal adenoviral gene therapy with hBMPR2 reliably distributed hBMPR2 to resistance PAs, but did not ameliorate PAH. Depressed BMPR2 expression may be a marker of PAH but is not central to the pathogenesis of this model of PAH.