First, put mairix.el in your Emacs search path and put
(require 'mairix) into your .emacs file. Then, use
M-x customize-group RET mairix RET to set your
preferences for mairix.el. The most important items are Mairix
File Path, Mairix Search File and Mairix Mail Program.
The latter specifies which mail program should be used to display the
mairix search results. Currently, RMail, Gnus with mbox files, and VM
are supported. If you use Gnus with maildir or mh, use the native
Gnus back end nnmairix instead.
If you use another Emacs mail program which is not yet supported by mairix.el, it is pretty easy to integrate it. See Extending mairix.el, on how to integrate it into mairix.el.
Now you should be ready to go. See Using mairix.el, for the available commands.