Seven steps are required for the FRET analysis protocol: 1) Zeiss format lsm image opening, 2) background removal, 3) SBT correction (PFRET software), 4) ROI selection, 5) overlapping ROI removal, 6) Extract and processing of FRET related ROI data, and 7) plot charts and perform statistical analysis. Three of those steps in the Image J ROI selection macro are described in detail, including background removal (panel a), ROI selection (panel b) and removal of overlapping ROIs (panel c).