BackgroundMagnetic particle imaging (MPI) is a recently developed, non‐invasive in vivo imaging technique to map the spatial distribution of superparamagnetic iron oxide nanoparticles (SPIONs) in animal tissues with high sensitivity and speed. It is a challenge to reconstruct images directly from the received signals of MPI device due to the complex physical behavior of the nanoparticles. System matrix and X‐space are two commonly used MPI reconstruction methods, where the former is extremely time‐consuming and the latter usually produces blurry images.PurposeCurrently, we proposed an end‐to‐end machine learning framework to reconstruct high‐resolution MPI images from 1‐D voltage signals directly and efficiently.MethodsThe proposed framework, which we termed “MPIGAN”, was trained on a large MPI simulation dataset containing 291 597 pairs of high‐resolution 2‐D phantom images and each image's corresponding voltage signals, so that it was able to accurately capture the nonlinear relationship between the spatial distribution of SPIONs and the received voltage signal, and realized high‐resolution MPI image reconstruction.ResultsExperiment results showed that, MPIGAN exhibited remarkable abilities in high‐resolution MPI image reconstruction. MPIGAN outperformed the traditional methods of system matrix and X‐space in recovering the fine‐scale structure of magnetic nanoparticles’ spatial distribution and achieving enhanced reconstruction performance in both visual effects and quantitative assessments. Moreover, even when the received signals were severely contaminated with noise, MPIGAN could still generate high‐quality MPI images.ConclusionOur study provides a promising AI solution for end‐to‐end, efficient, and high‐resolution magnetic particle imaging reconstruction.