Physics-based meso-scale models of fission gas behaviour for fuel performance codes currently consider only the average grain size as physical parameter to describe the fuel microstructure. Nevertheless, information on the grain-size distribution is available for several metallographically characterized fuel samples. To extend the current modelling approach, we present new experimental data and develop a methodology to treat the fuel grain-size distribution based on multi-grain analysis. This is applied to describe helium behaviour from infused and annealed polycrystalline UO2 samples. The methodology consists of three steps: (1) Acquisition of the empirical grain distribution from sections of the polycrystals, (2) Calculation of the gas di...