Background:The small molecule thrombolytic SMTP-7 excels in the treatment of ischemic stroke through an unidentified anti-inflammatory activity. Results: Affinity purification and inhibition studies reveal that SMTP-7 and its congeners inhibit soluble epoxide hydrolase (sEH), an enzyme responsible for inflammation. Conclusion: sEH is the plausible in vivo anti-inflammatory target of SMTP-7. Significance: Dual-targeting of thrombolysis and sEH is a promising strategy for novel stroke therapy.