A major building block of the future landscape of precision medicine will be nucleic acid therapeutics. However, the performance assessment of mRNA carriers is limited by two major challenges: (1) a lack of imaging technologies to detect nanocarriers and subsequent protein expression in whole organisms at a cell-level resolution, (2) a lack of analysis methods to precisely quantify the delivery of cargo/nanocarriers in whole-body. Researchers either use low-resolution tools to assess the whole-body distribution (e.g., bioluminescence, PET) or are forced to limit their analysis to a few predetermined targets with histological techniques with cellular resolution, limiting the understanding of the precise biodistribution and the efficiency. Here, we address this problem by cell-level imaging of mRNA in whole tissue-cleared mice. Specifically, we administered lipid nanoparticles encapsulating an EGFP-encoding mRNA labeled with a fluorophore to mice, used an adapted 3DISCO clearing protocol for whole body clearing, and employed light sheet imaging to determine the mRNA biodistribution and the efficiency. For quantitative analysis, we used an AI-based image analysis pipeline automatically extracting body-wide distributions of the mRNA and the EGFP-expressing cells. We detected and quantified mRNA biodistribution at clinically used doses, which is 1000-fold lower than the existing whole-body imaging methods. Additionally, our LNP biodistribution analysis pipeline was found compatible with whole-body antibody staining, which allows for localization of target regions. With our method, it is possible to systematically screen the effects of injection routes or different nanocarriers at a whole-body scale, providing a way to develop more precise nucleic acid delivery platforms.