Bone fracture treatments using Ilizarov circular fixator (ICF) involve dealing with uncertainties about a range of critical factors that control the mechanical microenvironment of the fracture site such as ICF configuration, fracture gap size, physiological loading etc. To date, the effects of the uncertainties about these critical factors on the mechanical microenvironment of the fracture site have not been fully understood. The purpose of this study is to tackle this challenge by using computational modelling in conjunction with engineering reliability analysis. Particularly, the effects of uncertainties in fracture gap size (GS), level of weight-bearing (P), ICF wire pretension (T) and wire diameter (WD) on the fracture site mechanical microenvironment at the beginning of the reparative phase of healing was investigated in this study. The results show that the mechanical microenvironment of fracture site stabilised with ICF is very sensitive to the uncertainties in P and GS. For example, an increase in the coefficient of variation of P (COVP ) from 0.1 to 0.9 (i.e., an increase in the uncertainty in P) could reduce the probability of achieving a favourable mechanical microenvironment within the fracture site (i.e., Probability of Success, PoS) by more than 50%, while an increase in the coefficient of variation of GS (COVGS ) from 0.1 to 0.9 could decrease PoS by around 30%. In contrast, an increase in the uncertainties in T and WD (COV increase from 0.1 to 0.9) has little influence on the fracture site mechanical microenvironment (PoS changes <5%).