Background:Laghupanchamula denotes combinations of roots of five herbs. However, in Ayurvedic classics besides four common herbs viz. Kantakari, Brihati, Shaliparni, and Prinshniparni, the fifth one is either Gokshura (Laghupanchamula with Gokshura LPG) or Eranda (Laghupanchamula with Eranda LPE), and both formulations have been documented to have shothahara (anti-inflammatory) action.Objectives:The present study was undertaken to compare the anti-inflammatory activity of 50% ethanolic extract of LPG (LPGE) and LPE (LPEE) in rats and safety in mice.Materials and Methods:LPGE and LPEE were given orally, administered either just before or 60 min before experiment on mice and for 7 days to rats. Paw edema was induced by carrageenan (acute) and formalin (sub-acute), whereas granuloma pouch (sub-acute) was induced by turpentine in rats.Results:Both LPGE and LPEE (1.0 g/kg) at 3 h after their administration showed inhibition of formalin-induced paw edema by 46.2% and 44.3% (P < 0.001) and carrageenan-induced paw edema by 53.9% and 60.4% (P < 0.001), respectively. After 7 days of treatment, both LPGE and LPEE showed 26.3% (P < 0.01) and 32.5% (P < 0.05) inhibition, respectively, against formalin-induced paw edema, and reduced weight of turpentine-induced granuloma pouch by 42.8% and 36.1% (P < 0.001), and volume of exudates by 31.2% and 36.2% (P < 0.001), respectively. No acute toxicity was observed in mice even with a 10.0-g/kg dose of both extracts.Conclusion:LPGE and LPEE significantly reduced acute and sub-acute inflammation, and showed effective and similar anti-inflammatory activity. They seemed to be safe, and use of both formulations in the Laghupanchamula for their anti-inflammatory activity is, thus, authenticated.