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 cirrhotic PHT in rats. Materials and methods: Seventy adult male albino rats were divided into 7 groups. Group I: control group, Group II: CCl4 untreated group, Group III: treated with propranolol at dose of 75mg/kg with CCl4, Groups IV, V and VI: treated with portulaca oleracea extract at doses of 0.05, 0.1, and 0.15 g/kg with CCl4, Group VII: treated with portulaca oleracea 0.15 g/kg plus propranolol 75 mg/kg with CCl4. After 12 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 doses of 0.1& 0.15 gm/kg, propranolol and portulaca oleracea 0.15 g/kg-propranolol combination significantly decreased the elevated portal pressure when compared to CCl4 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 hepatic histopathological score of both fibrosis (staging) and necrosis (grading) when compared to CCl4 group. Propranolol alone produced non-significant improvement in hepatic histopathological score of fibrosis (staging), liver enzymes, hepatic oxidative stress markers levels as well as hepatic level of IL-10 when compared to CCl4 group. CONCLUSION: Portulaca oleracea may be effective in the treatment of CCl4 induced PHT. This is probably mediated through its anti-inflammatory and antioxidant properties.