Abstract: A multi-phase equilibrium model consisted of multi-metal ion and low molecular mass ligands in human interstitial fluid were constructed to discuss the speciation of UO₂²⁺. Computer simulations indicated that the major UO₂²⁺ species were UO₂(CO₃)₃^4- and ，UO₂(CO₃)₂^2- at pH >7.0, and the major species were UO₂HPO₄ and UO₂(H₂PO₄)₂ at pH<6.0 when U was 1.5 μmol/L in H₂OCO₃^2--PO₄^3- model, whereas, the major species was solid (UO₂)₃(PO₄)₂ at pH3~6 when U was 0.15 mmol/L. Speciation study showed that UO₂²⁺ existed mainly in the forms of UO₂(CO₃)₃^4-, ，UO₂(CO₃)₂^2- and UO₂Cit₂^4- at pH>7.0 and in the form of UO₂Cit₂^4- at pH<6.0 when U was 1.5 μmol/L, and the major species was solid (UO₂)₃（PO₄)₂ at pH 3~6 when U was 0.15 mmol/L. The percentage of UO₂(CO₃)₃^4- increased with the CO₃^2- while the percentage of ，UO₂(CO₃)₂^2- and UO₂Cit₂^4- decreased with higher CO₃^2- whenever the U was 1.5 μmol/L or 0.15 mmol/L. The UO₂²⁺ was not chelated with NTA despite of its speciation was inflected when NTA was in the interstitial fluid model. The dominant species was UO₂Cit₂^4- when high concentration NTA in the interstitial fluid model when U was 1.5 μmol/L, and the major species was UO₂(CO₃)₃^4- when U was 0.15 mmol/L.