OBJECTIVE： To investigate the potential molecular mechanism of Epimedium brevicornu in the treatment of osteoarthritis based on “ingredient-target-pathway” network mode. METHODS： The potential active components in blood [pharmacokinetic parameters as oral drug bioavailability （OB）≥30％ and drug-likeness （DL）≥0.18] and target spots of E. brevicornu were screened and predicted by TCM system pharmacology database and analysis platform. The target spots of osteoarthritis were excavated from disease-related database， and key target spots of E. brevicornu in the treatment of osteoarthritis were screened by Topology analysis. The potential molecular mechanism of it was analyzed by using ClueGo analysis. RESULTS： A total of 130 corresponding compounds of E. brevicornu were retrieved in the study； 23 active compounds were screened according to OB and DL value， which predicted 102 potential target spots， the relationship networks of “the active components in blood-disease target” was structured. A total of 168 targets spots related to osteoarthritis were retrieved from disease-related database， and 185 key nodes were screened out by topological analysis. ClueGo analysis showed that signaling pathways involved in the action of E. brevicornu on osteoarthritis were mainly enriched in 68 signaling pathways such as cell cycle， inflammation and cancer related signaling pathways. The potential mechanism is that control the progress of disease to participate in the proliferation， apoptosis and differentiation of cartilage cells directly， regulate bone metabolism balance， and regulate the inflammation system， immune system and etc. to interfere with and influence bone and cartilage microenvironment. CONCLUSIONS： For osteoarthritis， E. brevicornu has the characteristics of multiple systems， multiple targets and multiple components. It is consistent with the current mechanism of osteoarthritis treatment.