BACKGROUND Mazaryun (Daphne oleoides Schreb.) is used as an anti-inflammatory drug in Unani medicine after detoxification, as it is defined under fourth-degree drugs. OBJECTIVE To evaluate and compare the anti-inflammatory activity of crude and detoxified Mazaryun in maximum and minimum doses. METHODS Anti-inflammatory activity was carried out by carrageenan-induced paw edema test. Wistar rats of either sex, weighing 150-200 gm, were divided into seven groups (I, II, IIIA, IIIB, IVA, IVB, and V) of six animals in each. Group I - plain control, administered with 1 ml of 1% CarboxyMethyl Cellulose (CMC); Group II - standard control, given Diclofenac Sodium (6 mg/kg); Group III - crude Mazaryun and Group IV - detoxified Mazaryun, A and B are maximum and minimum doses of test drug, respectively; and V group - positive control was not treated with any other drugs. The data was statistically analyzed by ANOVA repeated for inter-group analysis and ANOVA one-way for intra-group analysis with post hoc Tukey Kramer multiple comparison test. The GC-MS analysis of crude and detoxified leaves of Mazaryun was also carried out in continuation of study to determine the phytochemical changes before and after detoxification. RESULTS Maximum dose of detoxified Mazaryun and standard control groups showed significant anti-inflammatory activity at p < 0.001, and detoxified Mazaryun showed dose-dependent activity. The GC-MS fingerprints showed totally eight different chemical constituents in its crude and detoxified form. CONCLUSIONS The study standardised the concept of detoxication in Unani medicine, as the detoxified Mazaryun showed significant anti-inflammatory activity and present of totally different chemicals constituents.