Good understanding of blistering and embrittlement mechanism depends on good investigation of surface and internal microstructure damage of gas-ion-irradiated materials. Internal and surface microstructure of He+ ion irradiated CLAM steel were examined by cross-sectional transmission electron microscopy combining focused ion beam. Variation of helium bubble density and size distribution versus depth in CLAM steel after high dose helium irradiation at room temperature was investigated. The average size of helium bubble increased within 100–400 nm but decreased near the non-irradiated matrix with the increase of depth, while the density followed a reverse trend. The formation and growth mechanism of helium bubble is different at different irradiation depth. The formation of a zone of large bubbles under the surface is the main reason of surface blistering and flaking. Helium induced irradiation swelling and surface blistering at low temperature were also discussed.