Objective: This study aimed to reduce inflammation effect caused by long-term and large amount of betel nut chewing. Methods: Natural plant extracts with anti-inflammatory effects were added to betel nut in order to reduce the inflammatory damage. Glycyrrhiza uralensis fisch, radix platycodi and loquat leaf were used to treat rats with areca nut for 28 days. Body weight, organ coefficient, swelling rate of plantar in 6 hours, levels of inflammatory factors, and mediators were compared. Results: The addition of high-dose natural plant extract significantly reduced the production of prostaglandin E₂ (PGE₂), malondialdehyde (MDA), and nitric oxide (NO) compared to betel nut used group. Less pro-inflammatory tumor necrosis factor (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6) and more release of interleukin-10 (IL-10) were observed. It also reduced the production of reactive oxygen species (ROS) in the liver. The swelling rate of rats' feet (P＜0.05) was significantly lower than the control group, and similar to the positive control group. Conclusion: The addition of natural plant extracts with anti-inflammatory effect can reduce the acute inflammation in rats, and provide a new development idea for the further processing of areca catechu.