In this in vivo study, we found that the expression of P‐AKT in pulmonary vessels of rats with pulmonary hypertension induced by cigarette smoke was significantly increased, while the expression of P‐AKT in pulmonary vessels of rats in AAV1‐KLF4‐shRNA group was significantly lower than that in model groups. This evidence concerns the gene KLF4 and pulmonary hypertension.