Objective To study the neuroprotective effect of oridonin (Ori) regulating NLRP3 inflammasome expression in rats with intracerebral haemorrhage (ICH) and its possible mechanism. Methods The rats were randomly divided into sham operation group, model group, solvent group and treatment group by random number table method. ICH rat model was prepared by stereotactic injection of bacterial collagenase Ⅶ into the right caudate nucleus. After the intervention, neurological impairment was evaluated by mNSS on the 1st, 3rd and 7th day, cerebral water content was analyzed by dry-wet specific gravity method on the 1st and 3rd day, hematoxylin-eosin staining (HE) was used to observe pathological changes. The neuronal survival was analyzed by nissl staining, and IL-1β and IL-18 were detected by Enzyme-Linked immunosorbent assay (ELISA). The protein expressions of ASC, caspase-I and NLRP3 were detected by immunofluorescence and western blot (WB). Results The neurological deficits of the rats were improved by Ori treatment on day 3 and 7 (P＜0.05), but not on day 1 (P＞0.05). Compared with model group, brain edema was reduced (P＜0.05)，the number of viable neurons increased in treatment group at day 1 and 3 (P＜0.05). On day 3, the protein expression of ASC, caspase-Ⅰ and NLRP3 and the content of IL-1β and IL-18 were significantly decreased in treatment group (P＜0.05), but there was no significant difference in caspase-Ⅰ protein expression, IL-1β, IL-18 content on day (P＞0.05).Conclusion Oridonin can reduce neuroinflammatory response, cerebral edema, neuronal injury and neurological impairment in rats with ICH. The underlying mechanism can be realized by inhibiting the activation of NLRP3 inflammasome