We have a Network setup (WPMU) and I installed the plugin, activated it across the Network - and although you can't see it listed in the network sites under Plugins, it still works. No extra coding needed, I checked the source code and the email addresses are encoded.
The only issue I'm running into is for a custom plugin we have installed, it's not protecting those email addresses for some reason. It only protects the emails in regular pages and posts. So I'm guessing Custom Post Types may be a problem, otherwise it's a great plugin.
If there is a way to protect emails in custom post types, I'd be interested in hearing how to do that.