In this paper, a new content-based medical image retrieval (CBMIR) framework using an effective classification method and a novel relevance feedback (RF) approach are proposed. For a large-scale database with diverse collection of different modalities, query image classification is inevitable due to firstly, reducing the computational complexity and secondly, increasing influence of data fusion by removing unimportant data and focus on the more valuable information. Hence, we find probability distribution of classes in the database using Gaussian mixture model (GMM) for each feature descriptor and then using the fusion of obtained scores from the dependency probabilities, the most relevant clusters are identified for a given query. Afterwards, visual similarity of query image and images in relevant clusters are calculated. This method is performed separately on all feature descriptors, and then the results are fused together using feature similarity ranking level fusion algorithm. In the RF level, we propose a new approach to find the optimal queries based on relevant images. The main idea is based on density function estimation of positive images and strategy of moving toward the aggregation of estimated density function. The proposed framework has been evaluated on ImageCLEF 2005 database consisting of 10,000 medical X-ray images of 57 semantic classes. The experimental results show that compared with the existing CBMIR systems, our framework obtains the acceptable performance both in the image classification and in the image retrieval by RF.