Helium (He) is known to accumulate in vacancies of the steel structure materials of nuclear reactors, forming bubbles that increase in size and eventually cause structural problems, such as embrittlement. Several studies provided insights into the interstitial diffusion of this gas inside the iron matrix. However, much is still unknown about its behaviour. Based on this context, this study proposes a new combined theoretical and experimental multiscale approach made by the same team in a complementary way. It helps to have a global view of the helium diffusion in iron as a function of He content, temperature and structural defect concentration. Firstly, density functional theory has been used to identify the possible helium insertion sites in iron and the possible transitions between them. Then, the kinetic Monte Carlo method was applied to calculate its interstitial diffusion coefficient. It showed that helium swiftly diffuses interstitially in iron. It also tends to be trapped in iron vacancies and accumulate. The chromium and vacancy effects were also investigated. Experimentally, He was ion-implanted in several pure iron and high-purity Fe10wt%Cr samples. An analysis of He behaviour and its diffusion was carried out with transmission electron microscopy (TEM) and thermo-desorption spectroscopy (TDS) techniques. TEM shows the presence of small (∼0.7 nm radius) He bubbles and no significant difference with the presence of Cr. TDS evidences sequential “burst-type” He releases as T is sequentially increased. Based on these observations and inferred from the literature, we propose that He is detrapped and released from the studied materials as a consequence of the decrease in maximum He capacity of the trapping aggregates as T increases.