The equatorial and tropical regions of Africa are home to the hydrophyte Pistia stratiotes, which is a member of the Araceae family. Recent interest in the potential therapeutic advantages of medicinal plants has been amplified by the presence of their inherent bioactive components. The purpose of this in vivo investigation was to determine whether Pistia stratiotes possesses anti-inflammatory properties. The effect of Pistia stratiotes extract on inflammation in rats was investigated. To categorize the rats, five sets of five rats were utilized each time. The experimental groups consisted of the following: a positive control group, a normal control group, a low-dose group (200 mg/kg), a high-dose group (400 mg/kg), and an 80 mg/kg diclofenac group. The anti-inflammatory effects were assessed through the utilization of the carrageenan-induced paw edema technique. The results demonstrate that the extract significantly decreases the production of edema. The high dose (400 mg/kg) shows a remarkable inhibition of 61.1%, surpassing both the low dose (28.5%) and the positive control (0.0%). The extract exhibits substantial anti-inflammatory properties, similar to diclofenac (73.0%). The results indicate that the ethanolic extract of Pistia stratiotes exhibits strong anti-inflammatory properties, making it a promising candidate for the treatment of inflammatory disorders. This study indicates an additional clinical trial and developing formulations to fully realize the medicinal potential of the plant.