Background and aim: portal hypertension (PHT) is a common complication of liver cirrhosis and/or fibrosis. Propranolol is a nonselective beta blocker that is commonly used to reduce portal pressure. Portulaca oleracea extract has been shown to have hepatoprotective properties. The aim of this study is to assess the effects and interactions of portulaca oleracea extract and propranolol in non-cirrhotic PHT in rats. Materials and methods: eighty adult male albino rats were divided into 8 groups. Group I: control group, Group II: sham group, Group III: PPVL untreated group, Group IV: treated with propranolol at dose of 75mg/kg with PPVL, Groups V, VI and VII: treated with portulaca oleracea extract at doses of 0.05, 0.1, and 0.15 g/kg with PPVL, Group VIII: treated with portulaca oleracea 0.15 g/kg plus propranolol 75 mg/kg with PPVL. After 10 weeks, the portal pressure was measured in all groups then rats were sacrificed and blood samples were collected for estimation of liver enzymes (ALP, AST & ALP) levels then hepatic tissues were obtained for estimation of oxidative stress markers (MDA & SOD) and inflammatory markers (TNF-α, IL-6 & IL-10) as well as histopathological examination. Results: Portulaca oleracea extract at dose of 0.15 gm/kg, propranolol and portulaca oleracea 0.15 g/kg-propranolol combination significantly decreased the elevated portal pressure when compared to PPVL group. Portulaca oleracea alone, and in combination with propranolol significantly improved ALT, AST, ALP, MDA, SOD, TNF-α, IL-6, IL-10 levels as well as histopathological score of hepatic necrosis (grading) when compared to PPVL group. Propranolol alone produced non-significant improvement in liver enzymes, hepatic oxidative stress markers levels as well as hepatic level of IL-10 when compared to PPVL group.