Background/Introduction: Irrigation of root canal system is one of the most important steps in endodontic treatment. Combining different irrigants may modify the efficiency of the irrigation in removing organic and inorganic debris during biomechanical preparation. Aim/Objective: The aim of the study was to determine the chemical interaction that occurs during combination of various irrigating solutions and its effect on tissue dissolution. Materials : Muscle tissue samples of equal dimensions with their initial weights were taken and the samples were immersed in saline, sodium hypochlorite, ethylene diamine tetra acetic acid(EDTA), etidronic acid/1-hydroxyethane 1,1-diphosphonic acid(HEDP), ethylene glycol bis –N N N N’ – tetraacetic acid(EGTA)separately and in combinations of these agents for 5, 10 & 15 minutes. Results: Maximum tissue dissolving capacity was shown by sodium hypochlorite followed by sodium hypochlorite and HEDP combination, sodium hypochlorite and EGTA combination, sodium hypochlorite and EDTA combination. HEDP, EGTA, EDTA, and saline solutions when used alone did not show any tissue dissolving property. Conclusion: Sodium hypochlorite either alone or in combination with HEDP and EGTA maintains adequate available chlorine which could be the reason for its high efficiency.